Phosphorylation of Alzheimer disease amyloid precursor peptide by protein kinase C and Ca sup 2+ /calmodulin-dependent protein kinase II

Journal Article · Mon Aug 01 00:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.16.6218· OSTI ID:5405760

Gandy, S; Czernik, A J; Greengard, P ^[1]

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1. Rockefeller Univ., New York, NY (USA)

The amino acid sequence of the Alzheimer disease amyloid precursor (ADAP) has been deduced from the corresponding cDNA, and hydropathy analysis of the sequence suggest a receptor-like structure with a single transmembrane domain. The putative cytoplasmic domain of ADAP contains potential sites for serine and threonine phosphorylation. In the present study, synthetic peptides derived from this domain were used as model substrates for various purified protein kinases. Protein kinase C rapidly catalyzed the phosphorylation of a peptide corresponding to amino acid residues 645-661 of ADAP. Ca{sup 2+}/calmodulin-dependent protein kinase II phosphorylated ADAP peptide (645-661) on Thr-654 and Ser-655. Using rat cerebral cortex synaptosomes prelabeled with {sup 32}P{sub i}, a {sup 32}P-labeled phosphoprotein of {approx}135 kDa was immunoprecipitated by using antisera prepared against ADAP peptide(597-624), consistent with the possibility that the holoform of ADAP in rat brain is a phosphoprotein. Based on analogy with the effect of phosphorylation by protein kinase C of juxtamembrane residues in the cytoplasmic domain of the epidermal growth factor receptor and the interleukin 2 receptor, phosphorylation of ADAP may target it for internalization.

• OSTI ID: 5405760
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:16; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
NERVOUS SYSTEM DISEASES
PATHOGENESIS
PEPTIDES
AMINO ACID SEQUENCE
PHOSPHOTRANSFERASES
BIOCHEMISTRY
ADULTS
AGE DEPENDENCE
BRAIN
INFANTS
PHOSPHORUS 32
PHOSPHORYLATION
RATS
RECEPTORS
SERINE
SUBSTRATES
THREONINE
AGE GROUPS
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
CHEMISTRY
CHILDREN
DAYS LIVING RADIOISOTOPES
DISEASES
ENZYMES
HYDROXY ACIDS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
RADIOISOTOPES
RODENTS
TRANSFERASES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques